Encyclopedia
Exostosin glycosyltransferase 1
- genes
1. Normal Function
The EXT1 gene provides instructions for producing a protein called exostosin-1. This protein is found in a cell structure called the Golgi apparatus, which modifies newly produced enzymes and other proteins. In the Golgi apparatus, exostosin-1 attaches (binds) to another protein, exostosin-2, to form a complex that modifies heparan sulfate. Heparan sulfate is a complex of sugar molecules (a polysaccharide) that is added to proteins to form proteoglycans, which are proteins attached to several sugars. Heparan sulfate is involved in regulating a variety of body processes including blood clotting and the formation of blood vessels (angiogenesis). It also has a role in the spreading (metastasis) of cancer cells.
2. Health Conditions Related to Genetic Changes
2.1 Hereditary Multiple Osteochondromas
About 480 mutations in the EXT1 gene have been identified in people with hereditary multiple osteochondromas type 1, a condition in which people develop multiple benign (noncancerous) bone tumors called osteochondromas. Most of these mutations are known as "loss-of-function" mutations because they prevent any functional exostosin-1 protein from being made. The loss of functional exostosin-1 protein prevents it from forming a complex with the exostosin-2 protein and adding heparan sulfate to proteins. It is unclear how this impairment leads to the signs and symptoms of hereditary multiple osteochondromas.
2.2 Trichorhinophalangeal Syndrome Type II
The EXT1 gene is located in a region of chromosome 8 that is deleted in people with trichorhinophalangeal syndrome type II (TRPS II). TRPS II is a condition that causes bone and joint malformations including multiple osteochondromas (described above); distinctive facial features; intellectual disability; and abnormalities of the skin, hair, teeth, sweat glands, and nails. As a result of this deletion, affected individuals are missing one copy of the EXT1 gene in each cell. A shortage of exostosin-1 protein causes the osteochondromas in people with TRPS II. The deletion of other genes near the EXT1 gene likely contributes to the additional features of this condition.
3. Other Names for This Gene
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exostoses (multiple) 1
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exostosin 1
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EXT
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EXT1_HUMAN
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Glucuronosyl-N-acetylglucosaminyl-proteoglycan 4-alpha-N- acetylglucosaminyltransferase
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N-acetylglucosaminyl-proteoglycan 4-beta-glucuronosyltransferase
This entry is adapted from the peer-reviewed paper https://medlineplus.gov/genetics/gene/ext1
References
- Francannet C, Cohen-Tanugi A, Le Merrer M, Munnich A, Bonaventure J,Legeai-Mallet L. Genotype-phenotype correlation in hereditary multiple exostoses.J Med Genet. 2001 Jul;38(7):430-4.
- Lonie L, Porter DE, Fraser M, Cole T, Wise C, Yates L, Wakeling E, Blair E,Morava E, Monaco AP, Ragoussis J. Determination of the mutation spectrum of theEXT1/EXT2 genes in British Caucasian patients with multiple osteochondromas, and exclusion of six candidate genes in EXT negative cases. Hum Mutat. 2006Nov;27(11):1160.
- Maas S, Shaw A, Bikker H, Hennekam RCM. Trichorhinophalangeal Syndrome. 2017Apr 20. In: Adam MP, Ardinger HH, Pagon RA, Wallace SE, Bean LJH, Stephens K,Amemiya A, editors. GeneReviews® [Internet]. Seattle (WA): University ofWashington, Seattle; 1993-2020. Available fromhttp://www.ncbi.nlm.nih.gov/books/NBK425926/
- Maas SM, Shaw AC, Bikker H, Lüdecke HJ, van der Tuin K, Badura-Stronka M,Belligni E, Biamino E, Bonati MT, Carvalho DR, Cobben J, de Man SA, Den HollanderNS, Di Donato N, Garavelli L, Grønborg S, Herkert JC, Hoogeboom AJ, Jamsheer A,Latos-Bielenska A, Maat-Kievit A, Magnani C, Marcelis C, Mathijssen IB, NielsenM, Otten E, Ousager LB, Pilch J, Plomp A, Poke G, Poluha A, Posmyk R, RieublandC, Silengo M, Simon M, Steichen E, Stumpel C, Szakszon K, Polonkai E, van denEnde J, van der Steen A, van Essen T, van Haeringen A, van Hagen JM, Verheij JB, Mannens MM, Hennekam RC. Phenotype and genotype in 103 patients withtricho-rhino-phalangeal syndrome. Eur J Med Genet. 2015 May;58(5):279-92. doi:10.1016/j.ejmg.2015.03.002.
- McCormick C, Duncan G, Goutsos KT, Tufaro F. The putative tumor suppressorsEXT1 and EXT2 form a stable complex that accumulates in the Golgi apparatus andcatalyzes the synthesis of heparan sulfate. Proc Natl Acad Sci U S A. 2000 Jan18;97(2):668-73.
- Wuyts W, Van Hul W, De Boulle K, Hendrickx J, Bakker E, Vanhoenacker F,Mollica F, Lüdecke HJ, Sayli BS, Pazzaglia UE, Mortier G, Hamel B, Conrad EU,Matsushita M, Raskind WH, Willems PJ. Mutations in the EXT1 and EXT2 genes inhereditary multiple exostoses. Am J Hum Genet. 1998 Feb;62(2):346-54.
